Cardiovascular disease is the leading cause of mortality in the US, accounting for 45% of all deaths. Chronic Heart Failure (CHF) is now understood to be a multi-system disease process which involves not only the cardiovascular system but also the renal, neuroendocrine and immune systems. There is no effective therapy currently available to treat the most severe subset of CHF patients with acute decompensated HF. An unconventional approach to reduce the cardiodepressant effects associated with the chronic inflammatory state of CHF may provide a breakthrough therapy for this disorder. This proposal will evaluate the efficacy of an immunomodulatory device in a canine CHF model to identify opportunities for translation to clinical applications and eventual commercialization. The Product: The Biomimetic Membrane Device (BMD) is an immunoregulating, extracorporeal fiber membrane device targeted to modulate the cardiodepressant effects that are associated with CHF. BMD is a platform technology focused on immunomodulation of the acute and chronic inflammation associated with acute and chronic organ dysfunction. BMD polysulfone fibers selectively sequester activated systemic leukocytes as they flow through the fiber casing via an extracorporeal circuit. In preliminary studies, the BMDCHF has shown promising therapeutic benefit in a canine model of CHF. In- novation: In regard to current HF therapeutic strategies, the BMDCHF is a totally different, innovative approach to treat CHF. Rather than utilizing small pharmacologic molecules to improve myocardial contractility, the BMDCHF acts as an immunomodulatory device to dampen the cardio-depressant effects of the chronic pro- inflammatory state of CHF. Long Term Goal: This proposal will provide proof-of-concept for impact of the BMDCHF on CHF for up to 4 weeks post therapy. Phase I Hypothesis: The planned experiments will demonstrate improvement of cardiovascular performance after multiple 6 hour BMDCHF therapy sessions in a canine model of CHF. Aim 1: Assess impact of 3 x 6 hour BMDCHF sessions in a canine model of CHF at 48 hours post therapy. Aim 2: Assess BMDCHF therapy in a canine model of CHF at 1 and 4 weeks post therapy. Phase II Objective: The Phase II plan will assess BMDCHF optimal dose (with respect to number and length of sessions) and long term impact (3 -6 months) of therapeutic effect on cardiovascular and inflammatory parameters in a canine model of CHF. Commercial Opportunity: The data generated during the course of the Phase I and II study plans will be incorporated into the pre-clinical section of an IDE submission to the FDA for testing of the BMDCHF in the treatment of CHF. The market for these indications exceeds $30b annually in the US alone.